Parental terminal cancer and dependent children: a systematic review

Background When a parent has terminal cancer, their children are part of that experience. Parents often want to protect their children from their disease and prognosis. Knowledge of dependent children’s experience will help ensure they receive appropriate support. To date, there is lack of synthesis of this evidence examining children’s perspectives. Objectives To systematically search and synthesise the qualitative literature exploring the experiences of dependent children when their parent has terminal cancer. Methods Databases of MEDLINE, Embase, PsycINFO, CINAHL, Assia and the Cochrane library were searched systematically from inception to July 2020 to determine eligible studies. Included studies were appraised for quality and thematically synthesised using Thomas and Harden’s thematic synthesis framework. Results Fourteen studies were included, which interviewed children about their experiences (n=654 children aged 4–18 years at the time of parental death), from six countries. Five descriptive themes were identified, further categorised into two broad themes: (1) finding out about parental cancer and its impact on the family and (2) coping with life with parental cancer, death and beyond. Conclusion Children want to be involved in their parent’s cancer experience and to help support the family. Healthcare professionals are ideally placed to support and encourage parents to include their children. They should reassure parents that children can cope well and that maintaining normality will help, and explain the benefits of honest and open communication and how they can include dependent children from diagnosis and beyond

Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) for advanced pancreatic and periampullary adenocarcinoma

Long term prognosis and 5-year survival for pancreatic adenocarcinoma (PDAC) remains suboptimal. Endoscopic ultrasound (EUS) guided RFA (EUS-RFA) is an emerging technology and limited data exist regarding safety and long-term outcomes. The aim of this study is to report safety-profile, feasibility and outcomes of EUS-RFA for advanced PDAC. Prospective review of patients with diagnosis of locally-advanced or metastatic PDAC undergoing EUS-RFA between October 2016 to March 2018 with long-term follow up (\u3e 30 months). Study patients underwent a total of 1-4 RFA sessions. All patients were enrolled in longitudinal cohort study and received standard of care chemotherapy. 10 patients underwent EUS-RFA. Location of the lesions was in the head(4), neck(2), body(2), and tail(2). 22 RFA sessions were performed with a range of 1-4 sessions per patient. There were no major adverse events (bleeding, perforation, infection, pancreatitis) in immediate (up to 72 h) and short-term follow up (4 weeks). Mild worsening of existing abdominal pain was noted during post-procedure observation in 12/22 (55%) of RFA treatments. Follow-up imaging demonstrated tumor progression in 2 patients, whereas tumor regression was noted in 6 patients (\u3e 50% reduction in size in 3 patients). Median survival for the cohort was 20.5 months (95% CI, 9.93-42.2 months). Currently, 2 patients remain alive at 61 and 81 months follow-up since initial diagnosis. One patient had 3 cm PDAC with encasement of the portal confluence, abutment of the celiac axis, common hepatic and superior mesenteric artery. This patient had significant reduction in tumor size and underwent standard pancreaticoduodenectomy. In our experience, EUS-RFA was safe, well-tolerated and could be concurrently performed with standard chemotherapy. In this select cohort, median survival was improved when compared to published survival based upon SEER database and clinical trials. Future prospective trials are needed to understand the role of EUS-RFA in overall management of PDAC

A qualitative study of the experiences and expectations of women receiving in-patient postnatal care in one English maternity unit

Background Studies consistently highlight in-patient postnatal care as the area of maternity care women are least satisfied with. As part of a quality improvement study to promote a continuum of care from the birthing room to discharge home from hospital, we explored women’s expectations and experiences of current inpatient care. Methods For this part of the study, qualitative data from semi-structured interviews were transcribed and analysed using content analyses to identify issues and concepts. Women were recruited from two postnatal wards in one large maternity unit in the South of England, with around 6,000 births a year. Results Twenty women, who had a vaginal or caesarean birth, were interviewed on the postnatal ward. Identified themes included; the impact of the ward environment; the impact of the attitude of staff; quality and level of support for breastfeeding; unmet information needs; and women’s low expectations of hospital based postnatal care. Findings informed revision to the content and planning of in-patient postnatal care, results of which will be reported elsewhere. Conclusions Women’s responses highlighted several areas where changes could be implemented. Staff should be aware that how they inter-act with women could make a difference to care as a positive or negative experience. The lack of support and inconsistent advice on breastfeeding highlights that units need to consider how individual staff communicate information to women. Units need to address how and when information on practical aspects of infant care is provided if women and their partners are to feel confident on the woman’s transfer home from hospital

Radiofrequency Ablation Remodels the Tumor Microenvironment and Promotes Neutrophil-Mediated Abscopal Immunomodulation in Pancreatic Cancer

Pancreatic ductal adenocarcinoma (PDAC) presents a 5-year overall survival rate of 11%, despite efforts to improve clinical outcomes in the past two decades. Therapeutic resistance is a hallmark of this disease, due to its dense and suppressive tumor microenvironment (TME). Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) is a promising local ablative and potential immunomodulatory therapy for PDAC. In this study, we performed RFA in a preclinical tumor-bearing KrasG12D; Trp53R172H/+; Pdx1:Cre (KPC) syngeneic model, analyzed local and abscopal affects after RFA and compared our findings with resected PDAC specimens. We found that RFA reduced PDAC tumor progression in vivo and promoted strong TME remodeling. In addition, we discovered tumor-infiltrating neutrophils determined abscopal effects. Using imaging mass cytometry, we showed that RFA elevated dendritic cell numbers in RFA-treated tumors and promoted a significant CD4+ and CD8+ T-cell abscopal response. In addition, RFA elevated levels of programmed death-ligand 1 (PD-L1) and checkpoint blockade inhibition targeting PD-L1 sustained tumor growth reduction in the context of RFA. This study indicates RFA treatment, which has been shown to increase tumor antigen shedding, promotes antitumor immunity. This is critical in PDAC where recent clinical immunotherapy trials have not resulted in substantial changes in overall survival

Improving inpatient postnatal services: midwives views and perspectives of engagement in a quality improvement initiative

Background: despite major policy initiatives in the United Kingdom to enhance women's experiences of maternity care, improving in-patient postnatal care remains a low priority, although it is an aspect of care consistently rated as poor by women. As part of a systems and process approach to improving care at one maternity unit in the South of England, the views and perspectives of midwives responsible for implementing change were sought. Methods: a Continuous Quality Improvement (CQI) approach was adopted to support a systems and process change to in-patient care and care on transfer home in a large district general hospital with around 6000 births a year. The CQI approach included an initial assessment to identify where revisions to routine systems and processes were required, developing, implementing and evaluating revisions to the content and documentation of care in hospital and on transfer home, and training workshops for midwives and other maternity staff responsible for implementing changes. To assess midwifery views of the quality improvement process and their engagement with this, questionnaires were sent to those who had participated at the outset. Results: questionnaires were received from 68 (46%) of the estimated 149 midwives eligible to complete the questionnaire. All midwives were aware of the revisions introduced, and two-thirds felt these were more appropriate to meet the women's physical and emotional health, information and support needs. Some midwives considered that the introduction of new maternal postnatal records increased their workload, mainly as a consequence of colleagues not completing documentation as required. Conclusions: this was the first UK study to undertake a review of in-patient postnatal services. Involvement of midwives at the outset was essential to the success of the initiative. Midwives play a lead role in the planning and organisation of in-patient postnatal care and it was important to obtain their feedback on whether revisions were pragmatic and achieved anticipated improvements in care quality. Their initial involvement ensured priority areas for change were identified and implemented. Their subsequent feedback highlighted further important areas to address as part of CQI to ensure best quality care continues to be implemented. Our findings could support other maternity service organisations to optimise in-patient postnatal services

Revising acute care systems and processes to improve breastfeeding and maternal postnatal health: a pre and post intervention study in one English maternity unit

Background Most women in the UK give birth in a hospital labour ward, following which they are transferred to a postnatal ward and discharged home within 24 to 48 hours of the birth. Despite policy and guideline recommendations to support planned, effective postnatal care, national surveys of women’s views of maternity care have consistently found in-patient postnatal care, including support for breastfeeding, is poorly rated. Methods Using a Continuous Quality Improvement approach, routine antenatal, intrapartum and postnatal care systems and processes were revised to support implementation of evidence based postnatal practice. To identify if implementation of a multi-faceted QI intervention impacted on outcomes, data on breastfeeding initiation and duration, maternal health and women’s views of care, were collected in a pre and post intervention longitudinal survey. Primary outcomes included initiation, overall duration and duration of exclusive breastfeeding. Secondary outcomes included maternal morbidity, experiences and satisfaction with care. As most outcomes of interest were measured on a nominal scale, these were compared pre and post intervention using logistic regression. Results Data were obtained on 741/1160 (64%) women at 10 days post-birth and 616 (54%) at 3 months post-birth pre-intervention, and 725/1153 (63%) and 575 (50%) respectively postintervention. Post intervention there were statistically significant differences in the initiation (p = 0.050), duration of any breastfeeding (p = 0.020) and duration of exclusive breastfeeding to 10 days (p = 0.038) and duration of any breastfeeding to three months (p = 0.016). Post intervention, women were less likely to report physical morbidity within the first 10 days of birth, and were more positive about their in-patient care. Conclusions It is possible to improve outcomes of routine in-patient care within current resources through continuous quality improvement

A function-first approach to identifying formulaic language in academic writing

publication-status: Publishedtypes: ArticleThere is currently much interest in creating pedagogically-oriented descriptions of formulaic language. Research in this area has typically taken what we call a ‘form-first’ approach, in which formulas are identified as the most frequent recur- rent forms in a relevant corpus. While this research continues to yield valuable results, the present paper argues that much can also be gained by taking a ‘function-first’ approach, in which a corpus is first annotated for communicative functions and formulas are then identified as the recurrent patterns associated with each function. We demonstrate this approach through a comparative analysis of introductions to student essays and research articles. Focusing on one particularly com- mon communicative function, the analysis demonstrates that (1) this function is more common in student essays than in articles; (2) both the choice to use the function and the choice of linguistic forms that realize the function vary across sub- ject areas in research articles, but not in student essays; (3) research articles tend to be more formulaic in expressing the function than student essays; and (4) some parts of the forms used are highly formulaic, while others are more open. The key formulas are described and suggestions made regarding their pedagogical presentation

Lack of functional alpha-lactalbumin prevents involution in Cape fur seals and identifies the protein as an apoptotic milk factor in mammary gland involution

The mammary gland undergoes a sophisticated programme of developmental changes during pregnancy/lactation. However, little is known about processes involving initiation of apoptosis at involution following weaning. We used fur seals as models to study the molecular process of involution as these animals display a unique mammary gland phenotype. Fur seals have long lactation periods whereby mothers cycle between secreting copious quantities of milk for 2 to 3 days suckling pups on land, with trips to sea alone to forage for up to 23 days during which time mammary glands remain active without initiating apoptosis/involution.<br /

Both Noncoding and Protein-Coding RNAs Contribute to Gene Expression Evolution in the Primate Brain

Despite striking differences in cognition and behavior between humans and our closest primate relatives, several studies have found little evidence for adaptive change in protein-coding regions of genes expressed primarily in the brain. Instead, changes in gene expression may underlie many cognitive and behavioral differences. Here, we used digital gene expression: tag profiling (here called Tag-Seq, also called DGE:tag profiling) to assess changes in global transcript abundance in the frontal cortex of the brains of 3 humans, 3 chimpanzees, and 3 rhesus macaques. A substantial fraction of transcripts we identified as differentially transcribed among species were not assayed in previous studies based on microarrays. Differentially expressed tags within coding regions are enriched for gene functions involved in synaptic transmission, transport, oxidative phosphorylation, and lipid metabolism. Importantly, because Tag-Seq technology provides strand-specific information about all polyadenlyated transcripts, we were able to assay expression in noncoding intragenic regions, including both sense and antisense noncoding transcripts (relative to nearby genes). We find that many noncoding transcripts are conserved in both location and expression level between species, suggesting a possible functional role. Lastly, we examined the overlap between differential gene expression and signatures of positive selection within putative promoter regions, a sign that these differences represent adaptations during human evolution. Comparative approaches may provide important insights into genes responsible for differences in cognitive functions between humans and nonhuman primates, as well as highlighting new candidate genes for studies investigating neurological disorders

A novel 33-Gene targeted resequencing panel provides accurate, clinical-grade diagnosis and improves patient management for rare inherited anaemias

Accurate diagnosis of rare inherited anaemias is challenging, requiring a series of complex and expensive laboratory tests. Targeted next-generation-sequencing (NGS) has been used to investigate these disorders, but the selection of genes on individual panels has been narrow and the validation strategies used have fallen short of the standards required for clinical use. Clinical-grade validation of negative results requires the test to distinguish between lack of adequate sequencing reads at the locations of known mutations and a real absence of mutations. To achieve a clinically-reliable diagnostic test and minimize false-negative results we developed an open-source tool (CoverMi) to accurately determine base-coverage and the ‘discoverability’ of known mutations for every sample. We validated our 33-gene panel using Sanger sequencing and microarray. Our panel demonstrated 100% specificity and 99·7% sensitivity. We then analysed 57 clinical samples: molecular diagnoses were made in 22/57 (38·6%), corresponding to 32 mutations of which 16 were new. In all cases, accurate molecular diagnosis had a positive impact on clinical management. Using a validated NGS-based platform for routine molecular diagnosis of previously undiagnosed congenital anaemias is feasible in a clinical diagnostic setting, improves precise diagnosis and enhances management and counselling of the patient and their family